High throughput methods to measure the propensity of compounds to form intramolecular hydrogen bonding

Abstract

Implementation of IMHB considerations in drug discovery needs robust and validated descriptors to experimentally verify the propensity of compounds to exhibit IMHBs. The first part of the paper presents an overview of the most common techniques to measure the propensity of compounds to form IMHBs. Then we review and discuss recently proposed high throughput (HT) physicochemical descriptors (i.e. Δlog P_oct–tol, EPSA and log k′80 PLRP-S) which provide the same information. Analysis of the available data enabled us to extract guidelines for the application of these descriptors in drug discovery programs.